Dr. McKee was appointed as Assistant Professor of Surgery at the University of Chicago in July 2001. In the next five years, he will perform translational scientific research and initiate clinical trials based on a new immune therapy strategy for gastrointestinal malignancies. His research experience in tumor immunology, his environment at The University of Chicago, and the design of his appointment make him uniquely qualified to pursue these goals. Dr. McKee spent three years at the NCI performing clinical and laboratory research in tumor immunology, and his interest in gastrointestinal malignancies matured during a clinical fellowship in surgical oncology. In his proposed research, he will study the biology and genetics of T cells that recognize carcinoembryonic antigen (CEA). In so doing he will lay the foundation for clinical trials in patients with CEA-expressing tumors, including many colorectal, lung, breast, and pancreatic cancers. [unreadable] [unreadable] The University of Chicago has an established tumor immunology laboratory under the direction of Dr. Michael Nishimura, who was Dr. McKee's mentor at the NCI. In addition, a diverse and active immunology faculty provides a rich training environment and numerous opportunities for collaboration. The Department of Surgery has arranged a special appointment for Dr. McKee to foster his academic development in which 90% of his time will be protected from clinical activity until July 2003. Should he receive a K08 Research Career Award, Dr. McKee will utilize this supportive environment to continue his education in immunology, expand his technical capabilities, and complete a university curriculum in the responsible conduct of research. [unreadable] [unreadable] Under the mentorship of Dr. Nishimura, Dr. McKee will carry out a five-year research plan to determine whether lymphocytes transduced with genes for CEA specific T cell receptors will recognize and kill CEA-expressing tumors in vitro and in an animal model of human adenocarcinoma. Dr. McKee will identify and isolate human T lymphocytes that recognize MHC class I restricted peptides from carcinoembryonic antigen, sequence and clone T cell receptors from these lymphocytes, create retroviral constructs capable of transferring these genes to human and murine cells, and characterize these effectors in vitro and in vivo. By studying the interaction of these T cells and tumor cells in a detailed manner, he hopes to address problems that are faced by researchers investigating a broad range of current immunotherapy strategies. [unreadable] [unreadable]